Proteins That Promote Filopodia Stability, but Not Number, Lead to More Axonal-Dendritic Contacts

Dendritic filopodia are dynamic protrusions that are thought to play an active role in synaptogenesis and serve as precursors to spine synapses. However, this hypothesis is largely based on a temporal correlation between filopodia formation and synaptogenesis. We investigated the role of filopodia in synapse formation by contrasting the roles of molecules that affect filopodia elaboration and motility, versus those that impact synapse induction and maturation. We used a filopodia inducing motif that is found in GAP-43, as a molecular tool, and found this palmitoylated motif enhanced filopodia number and motility, but reduced the probability of forming a stable axon-dendrite contact. Conversely, expression of neuroligin-1 (NLG-1), a synapse inducing cell adhesion molecule, resulted in a decrease in filopodia motility, but an increase in the number of stable axonal contacts. Moreover, RNAi knockdown of NLG-1 reduced the number of presynaptic contacts formed. Postsynaptic scaffolding proteins such as Shank1b, a protein that induces the maturation of spine synapses, increased the rate at which filopodia transformed into spines by stabilization of the initial contact with axons. Taken together, these results suggest that increased filopodia stability and not density, may be the rate-limiting step for synapse formation

Germ Line Origin and Somatic Mutations Determine the Target Tissues in Systemic AL-Amyloidosis

BACKGROUND: Amyloid is insoluble aggregated proteins deposited in the extra cellular space. About 25 different proteins are known to form amyloid in vivo and are associated with severe diseases such as Alzheimer's disease, prion diseases and type-2 diabetes. Light chain (AL) -amyloidosis is unique among amyloid diseases in that the fibril protein, a monoclonal immunoglobulin light chain, varies between individuals and that no two AL-proteins with identical primary structures have been described to date. The variability in tissue distribution of amyloid deposits is considerably larger in systemic AL-amyloidosis than in any other form of amyloidosis. The reason for this variation is believed to be based on the differences in properties of the amyloidogenic immunoglobulin light chain. However, there is presently no known relationship between the structure of an AL-protein and tissue distribution. METHODOLOGY/PRINCIPAL FINDINGS: We compared the pattern of amyloid deposition in four individuals with amyloid protein derived from variable light chain gene O18-O8, the source of a high proportion of amyloidogenic light chains, and in whom all or most of the fibril protein had been determined by amino acid sequencing. In spite of great similarities between the structures of the proteins, there was a pronounced variability in deposition pattern. We also compared the tissue distribution in these four individuals with that of four other patients with AL-amyloid derived from the L2-L16 gene. Although the interindividual variations were pronounced, liver and kidney involvement was much more evident in the latter four. CONCLUSIONS/SIGNIFICANCE: We conclude that although the use of a specific gene influences the tissue distribution of amyloid, each light chain exhibits one or more determinants of organ-specificity, which originate from somatic mutations and post-translational modifications. Eventual identification of such determinants could lead to improved treatment of patients with AL amyloidosis

Scintillating bolometers based on ZnMoO4 and Zn100MoO4 crystals to search for 0ν2β decay of 100Mo (LUMINEU project): first tests at the Modane Underground Laboratory

The technology of scintillating bolometers based on zinc molybdate (ZnMoO4) crystals is under development within the LUMINEU project to search for decay of 100Mo with the goal to set the basis for large scale experiments capable to explore the inverted hierarchy region of the neutrino mass pattern. Advanced ZnMoO4 crystal scintillators with mass of ∼0.3 kg were developed and Zn100MoO4 crystal from enriched 100Mo was produced for the first time by using the low-thermal-gradient Czochralski technique. One ZnMoO4 scintillator and two samples (59 g and 63 g) cut from the enriched boule were tested aboveground at milli-Kelvin temperature as scintillating bolometers showing a high detection performance. The first results of the low background measurements with three ZnMoO4 and two enriched detectors installed in the EDELWEISS set-up at the Modane Underground Laboratory (France) are presented

: Thessalie

International audienc

: Gaule

International audienc

: Gaule

International audienc

Lentus Arar Rhodanusque ferox, ou les avatars d'une géographie fluviale

International audienceLes attestations les plus anciennes de la Saône et du Rhône n'associent pas les deux cours d'eau ; c'est seulement avec César que se crée le couple fluvial Saône-Rhône, qui apparaîtra fréquemment dans la littérature postérieure sous forme antithétique, le Rhône avec son impétuosité et son abondance, la Saône avec son calme. La conquête romaine améliore considérablement la reconnaissance du cours des fleuves d'Europe occidentale, de leurs sources à leurs embouchures. Cependant, on note une dégénérescence des représentations de ces cours dans des ouvrages tardifs, en particulier dans la Cosmographie de Julius Honorius, au 5e s. de notre ère, qui présente une géographie fluviale surprenante à laquelle on peut apporter deux explications : ce qui est décrit correspond moins au cours d'un fleuve qu'à une route commerciale, mais aussi resurgit une géographie mythique beaucoup plus ancienne, inspirée particul